Deoxynivalenol (DON), one of the most severely polluting mycotoxins globally, contaminates agricultural products and food through environmental pathways, compromising intestinal barrier integrity and homeostasis in humans and animals. This disruption triggers intestinal mucositis and exacerbates inflammatory bowel disease (IBD) progression. Current therapies focusing on immunosuppression face limitations due to drug resistance, shifting research toward mucosal healing strategies for sustained remission. Macrophages, essential mediators of intestinal immunity, exhibit metabolic and phenotypic plasticity critical for mucosal repair. Emerging evidence highlights nutrient-mediated metabolic reprogramming as a potential approach to enhance macrophage-driven mucosal healing and barrier restoration. This review synthesizes DON-induced intestinal toxicity mechanisms, discusses the complex functions of macrophages in intestinal mucosal healing, and highlights the current advances of nutrients regulation targeting macrophages to promote intestinal mucosal healing. Finally, feasible research directions for mitigating DON-related health risks through innovative nutritional strategies are proposed, emphasizing translational applications in food safety and precision nutrition.